Regulatory T Cells and Autoimmune Diseases - Chapter 19: Role of regulatory T cells in the pathogenesis and therapeutics of autoimmune hepatitis

Defects in regulatory T cells (Tregs), a lymphocyte subset key to the maintenance of immune homeostasis, play a permissive role in the perpetuation and progression of liver damage in autoimmune hepatitis (AIH), a severe hepatopathy characterized by hypergammaglobulinemia, serum autoantibodies and histological evidence of interface hepatitis. Treg defects in AIH include numerical impairment, reduced suppressive function, poor ability to respond to IL-2, and increased plasticity with the acquisition of effector properties. Restoring Tregs either through adoptive transfer of autologous Tregs or upon modulation of the inflammatory environment, would enable controlling inflammation while reestablishing immune tolerance. In this chapter, we review studies reporting the important role of Treg impairment in AIH pathogenesis and discuss methods to restore Treg pool and function. Challenges and potential caveats of these new immunotherapeutic approaches are also reviewed here.